Jan Niesing

Shortage of donation despite an adequate number of donors: A professional attitude?

Background. A major problem in the field of transplantation is the persistent shortage of donor organs and tissues for transplantation. This study was initiated to (1) chart the donor potential for organs and tissue in The Netherlands and (2) to identify factors influencing whether donation is discussed with next of kin. Methods. A registration form was constructed to obtain information at time of death of patients about the demographic characteristics, diagnosis, and medical suitability for donation. A prospective study was conducted among 11 hospitals in The Netherlands that gathered 4,877 filled-in forms equaling 8% to 10% of the people dying in a hospital in The Netherlands per year. Results. In the year of the study, organs were retrieved from 22 donors and tissues from 264 donors in the 11 hospitals. The organ potential is estimated at a maximum of 38.7 per million population per year. A mere 5% of the physicians got a 100% score on criteria and contraindications for donation. Factors of influence on receiving consent for donation were the will of the donor, using a protocol, giving verbal information to the relatives, and presence of the partner of the deceased patient. For 26% of the potential tissue donors and 69% of the potential organ donors, donation was discussed with the relatives. Consent for tissue donation was obtained in 27%, and consent for organ donation was obtained in 60%. Conclusions. In The Netherlands, when taking into account current refusal percentages, 320 to 360 organ donations and 5,800 tissue donations could be effectuated if organ donation is posed to all possible donors. For this, knowledge of medical criteria and contraindications for donation by the physicians and their willingness to discuss donation with next of kin must be improved.

UMOD as a susceptibility gene for end-stage renal disease

BackgroundIn recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.MethodsTo investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation.ResultsThe rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts.ConclusionsOur study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.

Matrix metalloproteinases as profibrotic factors in terminal ileum in Crohn's disease

Background: Returning stenosis in Crohns disease (CD) patients is poorly understood. After resection, newly developed strictures are seen within 10 years in 50% to 70%. Matrix metalloproteinases (MMPs) are involved in matrix‐turnover processes. This study analyzes spatial expression of MMP‐1, MMP‐3, MMP‐9, tissue inhibitor of MMP‐1, and collagen III to get better insight in tissue remodeling of terminal ileum of CD patients. Methods: Expressions were analyzed on mRNA and the protein level (MMP‐1, MMP‐3) in segments from resected terminal ileum from CD and control patients. In CD, macroscopic distinction was made between proximal resection margin, prestenotic, and stenotic tissue. Immunohistochemistry allowed for expression analyses transmurally. Results: MMP‐1 and MMP‐3 gene expression was up‐regulated (P < 0.05) in both prestenotic and stenotic tissue. MMP‐1 protein was significantly up‐regulated in submucosal and muscular tissue of prestenotic parts and in muscular tissue of stenotic Crohn samples. MMP‐3 protein was significantly up‐regulated in all layers of prestenotic and stenotic Crohn samples. Even in submucosa of proximal resection margin tissue, MMP‐3 expression was significantly higher than in controls. Conclusion: Surprisingly, in proximal resection margin tissue up‐regulated MMP‐3 was seen. This suggests that in nonresected terminal ileum, in which anastomosis is made, tissue turnover is present, which may account for the high recurrence of intestinal strictures.

SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation

Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FEcreat) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with (125)I-iothalamate clearance. Creatinine clearance was also assessed. FEcreat was calculated from the simultaneous clearances of creatinine and (125)I-iothalamate. Donor rs316009 was associated with FEcreat (beta -0.053, P = 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16-1.67], P = 0.00065, and 1.23 [1.02-1.48], P = 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD.

CUBN as a novel locus for end-stage renal disease: insights from renal transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys.

The role of personal characteristics in the relationship between health and psychological distress among kidney transplant recipients

Although kidney transplantation improves overall quality of life and physical functioning, improvements of psychological distress are often modest. However, apparent stressors such as comorbidity are only weakly associated with psychological distress and their impact differs considerably between patients. Wilson and Cleary proposed a theoretical model to explain these relationships. This model has been supported by research, but has never been applied in a population of kidney transplant recipients. Findings of the current study are based on a cross-sectional study carried out in 2008 in the northern Netherlands. An elaborated version of Wilson and Clearys model specifying hypothesized relationships of objective health, functional status, subjective health, personal characteristics and psychological distress was evaluated with structural equation modelling. After elimination of non-significant paths the final model provided a good fit for the data, X(2) (2)=4.23, p=0.12; RMSEA=0.047, CI(RMSEA) (0; 0.11); ECVI=0.060, ECVI(sat)=0.059. Results suggest that objective health has an indirect effect on psychological distress, in size comparable to the effects exerted by functional status and subjective health. Personal characteristics are the strongest determinant of psychological distress, but are directly and indirectly affected by objective health. Results indicate that poor health might cause psychological distress by increasing coping demands while simultaneously decreasing coping resources.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini‐open muscle splitting incision (MSI) technique and the transperitoneal hand‐assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0–44) vs. 15 (0–70), P = 0.043] and day 3 [7 (0–28) vs. 10 (0–91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0–73) vs. 42 (6–86), P = 0.001], day 7 [8 (0–66) vs. 33 (3–76), P < 0.001] and day 14 [2 (0–17) vs. 12 (0–51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND‐36, reduced costs and reduced CRP and IL‐6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy.

Are patient and relationship variables associated with participation of intimate partners in couples research

BACKGROUND Recruitment of participants for studies focusing on couples facing illness is a challenging task and participation decline may be associated with nonrandom factors creating bias. This study examines whether patient and relationship characteristics are associated with partner participation in research. METHOD Patients invited to participate in a cross-sectional study on adaptation and quality of life after renal transplantation were asked to forward information about an add-on study to their partners. RESULTS A total of 456 participating patients had a partner; 293 of the partners showed interest in the study and 206 actually completed the questionnaire. Backward logistic regression analyses revealed that demographic, illness, and personal characteristics of the patient were not associated with partner interest in the study nor actual partner participation. However, partners who indicated interest in the study showed more active engagement toward the patients (as reported by the patients). Furthermore, patients of partners who actually completed the questionnaire reported less negative affect and higher relationship satisfaction than patients whose partner did not participate in the study. DISCUSSION It is encouraging that of the large number of variables tested, only 2 were associated with the participation of partners. Nevertheless, well-functioning couples appear to be overrepresented in our study, calling for specific effort to include marital distressed couples in research focusing on dyadic adaptation to illness.

The making of a pan-European organ transplant registry

A European patient registry to track the outcomes of organ transplant recipients does not exist. As knowledge gleaned from large registries has already led to the creation of standards of care that gained widespread support from patients and healthcare providers, the European Union initiated a project that would enable the creation of a European Registry linking currently existing national databases. This report contains a description of all functional, technical, and legal prerequisites, which upon fulfillment should allow for the seamless sharing of national longitudinal data across temporal, geographical, and subspecialty boundaries. To create a platform that can effortlessly link multiple databases and maintain the integrity of the existing national databases crucial elements were described during the project. These elements are: (i) use of a common dictionary, (ii) use of a common database and refined data uploading technology, (iii) use of standard methodology to allow uniform protocol driven and meaningful long‐term follow‐up analyses, (iv) use of a quality assurance mechanism to guarantee completeness and accuracy of the data collected, and (v) establishment of a solid legal framework that allows for safe data exchange.

Urological Complications After Kidney Transplantation: Incidence And Risk-factors

Aims: The purpose of this study was to determine the incidence and management of urological complications. The possible risk factors from donor, graft and recipient for were ascertained for development of urological complications. Methods: Between 1992 and 2004, 974 patients underwent renal transplantation in our hospital. The patients with urological complications from this group were compared to a random sample of 357 patients without urological complications. Donor, graft and recipient characteristics, as well as implantantion procedure were scored. The incidence and type of complication were described and risk factors for urological complications were determined by chi-square tests and univariate analysis. Results: There were 78 (8.0 %) patients with urological complications. The complications were urinary leakage in 14 (1.4%), ureteral obstruction in 25 (2.6%), stenosis in 22 (2.3%) and hydronefrosis in 17 (1.7%). Age and cause of death were not related to urological complications. A relevant risk-factor for development of urological complications was mean systolic blood pressure of donor during last 24 hours. Two and threeway interactions were found for urine output in the last hour, systolic blood pressure and the occurence of hypotensive episodes. Ureter, venous and arterial abnormalities were not related to urological complications, nor were atherosclerosis, vascular problems or surgical bleeding. Conclusions: The incidence of urological complications was 8%. Urine output, systolic blood pressure and the occurence of hypotensive episodes of the donor combined have a strong additive effect on the occurence of urological complications. Donor and recipient characteristics and implantation problems showed no relation with the occurence of urological complications.